Rofecoxib pharmacokinetics and molecular data

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Phone:617-632-7753

Pharmacokinetics

Absorption

Food and Antacid Effects

Distribution

Metabolism

Excretion

Gender

Geriatric

Pediatric

Race

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Absorption

The mean oral bioavailability of VIOXX at therapeutically recommended doses of 12.5, 25 and 50 mg is approximately 93%. The area under the curve (AUC) and peak plasma level (Cmax) following a single 25 mg dose were 3286( ±843) ng*hr/mL and 207 (±111) ng/mL, respectively. Both Cmax and AUC are roughly dose proportional across the clinical dose range. At doses greater than 50 mg, there is a less than proportional increase in Cmax and AUC, which is thought to be due to the low solubility of the drug in aqueous media. Return to top

Food and Antacid Effects

Food had no significant effect on either the peak plasma concentration (Cmax) or extent of absorption (AUC) of rofecoxib when VIOXX tablets were taken with a high fat meal. The time to peak plasma concentration (Tmax), however, was delayed by 1 to 2 hours. The food effect on the suspension formulation has not been studied. VIOXX tablets can be administered without regard to timing of meals. Return to top

Distribution

Rofecoxib is approximately 87% bound to human plasma protein over the range of concentrations of 0.05 to 25 mg/mL. The apparent volume of distribution at steady state (Vdss) is approximately 91 L following a 12.5 mg dose and 86 L following a 25 mg dose. Return to top

Metabolism

Metabolism of rofecoxib is primarily mediated through reduction by cytosolic enzymes. The principal metabolic products are the cis-dihydro and trans-dihydro derivatives of rofecoxib, which account for nearly 56% of recovered radioactivity in the urine. An additional 8.8% of the dose was recovered as the glucuronide of the hydroxy derivative, a product of oxidative metabolism. The biotransformation of rofecoxib and this metabolite is reversible in humans to a limited extent (<5%). These metabolites are inactive as COX-1 or COX-2 inhibitors. Return to top

Excretion

Rofecoxib is eliminated predominantly by hepatic metabolism with little (<1%) unchanged drug recovered in the urine. Following a single radiolabeled dose of 125 mg, approximately 72% of the dose was excreted into the urine as metabolites, and 14% in the feces as unchanged drug. Return to top

Gender

The pharmacokinetics of rofecoxib are comparable in men and women. Return to top

Geriatric

After a single dose of 25 mg VIOXX in elderly subjects (over 65 years old) a 34% increase in AUC was observed as compared to the young subjects. Dosage adjustment in the elderly is not necessary; however, therapy with VIOXX should be initiated at the lowest recommended dose. Return to top

Pediatric

VIOXX has not been investigated in patients below 18 years of age. Return to top

Race

Meta-analysis of pharmacokinetic studies has suggested a slightly (10-15%) higher AUC of rofecoxib in Blacks and Hispanics as compared to Caucasians. No dosage adjustment is necessary on the basis of race. Return to top

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The content of this page is taken from the FDA package insert for this drug and should not be edited.